ABSTRACT
Using trifluoroacetyl sulfuric acid (TFAOSO3H), we discovered a new methane activation method and revealed its radical pathway under mild conditions. Upon the addition of a radical initiator with methane, the crude solution of TFAOSO3H developed the methyltrifluoroacetylsulfate radical ((TFAO)CH3S(OH)O2â¢). The resulting (TFAO)CH3S(OH)O2⢠behaved as a critical radical propagator for carbon-hydrogen bond activation, culminating in successful methane sulfonation. With 9.5 mol % of K2S2O8, TFAOSO3H and methane were selectively converted to methanesulfonic acid in 94 and 86% conversion yields, respectively.
Subject(s)
Methane , Free Radicals , Hydrogen Bonding , Methane/chemistryABSTRACT
Thorough mechanistic studies and DFT calculations revealed a background radical pathway latent in metal-catalyzed oxidation reactions of methane at low temperatures. Use of hydrogen peroxide with TFAA generated a trifluoromethyl radical (â¢CF3), which in turn reacted with methane gas to selectively yield acetic acid. It was found that the methyl carbon of the product was derived from methane, while the carbonyl carbon was derived from TFAA. Computational studies also support these findings, revealing the reaction cycle to be energetically favorable.
Subject(s)
Chlorofluorocarbons, Methane/chemistry , Methane/chemistry , Carbon-13 Magnetic Resonance Spectroscopy , Catalysis , Proton Magnetic Resonance SpectroscopyABSTRACT
A method has been developed for one-step ortho-selective ligand-directed H-D exchange, accompanied in some cases by concurrent acid-catalyzed electrophilic deuteration. This method is effective for deuteration of aromatic substrates ranging from ketones to amides and amino acids, including compounds of biological and pharmaceutical interest such as acetaminophen and edaravone. Use of a palladium catalyst featuring an NHC ligand is critical for the observed reactivity. Experimental evidence strongly suggests that palladium facilitates C-H activation of the aromatic substrates, a mechanism seldom observed under strongly acidic conditions. 2015 Elsevier Ltd. All rights reserved.
ABSTRACT
The H-D exchange of aromatic amines and amides, including pharmaceutically relevant compounds such as acetaminophen and diclofenac, was investigated using CF3COOD as both the sole reaction solvent and source of deuterium label. The described method is amenable to efficient deuterium incorporation for a wide variety of substrates possessing both electron-donating and electron-withdrawing substituents. Best results were seen with less basic anilines and highly activated acetanilides, reflecting the likelihood of different mechanistic pathways.
ABSTRACT
An efficient laboratory experiment has been developed for undergraduate students to conduct hydrogen-deuterium (H-D) exchange of resorcinol by electrophilic aromatic substitution using D2O and a catalytic amount of H2SO4. The resulting labeled product is characterized by 1H NMR. Students also visualize a significant kinetic isotope effect (kH/kD ≈ 3 to 4) by adding iodine tincture to solutions of unlabeled resorcinol and the H-D exchange product. This method is highly adaptable to fit a target audience and has been successfully implemented in a pedagogical capacity with second-year introductory organic chemistry students as part of their laboratory curriculum. It was also adapted for students at the advanced high school level.
ABSTRACT
The hydroamination of various substituted vinyl arenes with benzenesulfonamide was explored using an NHC-amidate-alkoxide palladium catalyst in conjunction with p-TsOH. Utilizing halide-substituted and electron-rich vinyl arenes, this methodology selectively furnished the cross-coupled hydroamination products in moderate to excellent yields in a Markovnikov fashion while greatly reducing undesired acid-catalyzed homocoupling of the vinyl arenes. Electron-rich vinyl arenes typically required milder conditions than electron-poor ones. While most effective for para-substituted substrates, the catalyst system also furnished the desired products from ortho- and meta-substituted vinyl arenes with high chemoselectivities.
ABSTRACT
Using our tridentate NHC-amidate-alkoxide Pd(II) complex, we developed a catalytic method for oxidative C-C bond cleavage of glycerol. The glycerol was degraded exclusively to formic acid and CO2. Two possible degradation pathways were proposed through 13C labeled studies.
ABSTRACT
Since the introduction of drug discovery based on single targets, the number of newly developed drugs has steadily declined, and the reliablility of the current drug-discovery paradigm has been unceasingly questioned. As an alternative, an emerging approach pursuing multi-targeting drugs has arisen to reflect multifactorial diseases caused by the complex networks of various mechanisms. The purpose of this paper is to review multi-target drugs and introduce our progress in establishing a practical methodology for identifying antinociceptive multi-target drugs. We have adopted a system of ex vivo efficacy screening using long-term potentiation in rat spinal cord as a surrogate biomarker for neuropathic pain. A bait-target approach is also adopted to lure an unknown target combination that induces synergistic mechanisms.
Subject(s)
Analgesics/therapeutic use , Disease Models, Animal , Pain/drug therapy , Analgesics/pharmacology , Animals , Drug Design , Humans , Pain/physiopathology , Rats , Spinal Cord/drug effects , Spinal Cord/physiopathologyABSTRACT
Oxidation of various carbohydrates to ammonium formate was investigated in the presence of hydrogen peroxide and ammonium hydroxide. Most of the examined carbohydrates except nonreducing sugars were efficiently converted into ammonium formate under environment friendly and mild conditions in aqueous media.
ABSTRACT
HIV-1 integrase (IN), one of the essential enzymes in HIV infection, has been validated as a target for HIV treatment. While more than 20 drugs have been approved by the FDA to treat HIV/AIDS, only one drug, Raltegravir (1), was approved as an IN inhibitor. The rapid mutation of the virus, which leads to multidrug resistant HIV strains, presents an urgent need to find potent compounds that can serve as second-generation IN inhibitors. The pyrazolone scaffold, predicted by a computational modeling study using GS-9137(2) as a pharmacophoric model, has shown to inhibit the IN catalytic activities in low micromolar range. We have synthesized various analogs based on the pyrazolone scaffold and performed SAR studies. This paper will showcase the up-to-date result of this scaffold as a promising HIV-1 IN inhibitor.
Subject(s)
HIV Integrase Inhibitors/pharmacology , Pyrazolones/pharmacology , Catalysis , HIV Integrase Inhibitors/chemistry , HIV-1/enzymology , HIV-1/genetics , Models, Molecular , Mutation , Pyrazolones/chemistry , Structure-Activity RelationshipABSTRACT
A palladium-catalyzed diacetoxylation of alkenes in the presence of peracetic acid and acetic anhydride was developed to produce diacetates efficiently and diastereoselectively. Due to its mild conditions, this method was suitable for a broad range of substrates encompassing conjugated and nonconjugated olefins.
Subject(s)
Acetic Anhydrides/chemistry , Alkenes/chemistry , Palladium/chemistry , Peracetic Acid/chemistry , Catalysis , Combinatorial Chemistry Techniques , Molecular Structure , StereoisomerismABSTRACT
Chiral dimeric tridentate NHC-amidate-alkoxide palladium(II) complexes, 3a and 3b, effected oxidative boron Heck-type reactions of aryl boronic acids with both acyclic and cyclic alkenes at room temperature to afford the corresponding coupling products with high enantioselectivities. The high degree of enantioselection, far superior to existing methods, stems from differences in the nonbonding interactions in the proposed transition states, due to the influence from bulky substituents of the alkene substrates and the "counter axial groups" of the palladium(II) catalysts.
Subject(s)
Alkenes/chemistry , Boron/chemistry , Boronic Acids/chemistry , Organometallic Compounds/chemistry , Oxides/chemistry , Palladium/chemistry , Catalysis , Cyclization , Kinetics , Ligands , Molecular Structure , Oxidation-Reduction , Stereoisomerism , Structure-Activity Relationship , TemperatureABSTRACT
Formal aromatic C-H insertion of rhodium(II) carbenoid was intensively investigated to develop a new methodology and probe its mechanism. Contrasting with the previously proposed direct C-H insertion, the mechanism was revealed to be electrophilic aromatic substitution, which was supported by substituent effects on the aromatic ring and a secondary deuterium kinetic isotope effect. Various isoquinolinones were synthesized intramolecularly via six-membered ring formation with high regio- and diastereoselectivity, while averting the common Buchner-type reaction. Intermolecularly, dirhodium catalyzed formal aromatic C-H insertion on electron-rich aromatics was also achieved.
Subject(s)
Carbon/chemistry , Hydrogen/chemistry , Isoquinolines/chemistry , Isoquinolines/chemical synthesis , Catalysis , Diazonium Compounds/chemistry , Kinetics , Models, Molecular , Molecular Conformation , Rhodium/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
A simple and efficient one-pot, three-component method has been developed for the synthesis of alpha-aminonitriles. This Strecker reaction is applicable for aldehydes and ketones with aliphatic or aromatic amines and trimethylsilyl cyanide in the presence of a palladium Lewis acid catalyst in dichloromethane solvent at room temperature.
Subject(s)
Aldehydes/chemistry , Amides/chemistry , Heterocyclic Compounds/chemical synthesis , Ketones/chemistry , Methane/analogs & derivatives , Palladium/chemistry , Catalysis , Heterocyclic Compounds/chemistry , Methane/chemistry , Molecular StructureABSTRACT
While developing novel catalysts for carbon-carbon or carbon-heteroatom coupling (N, O, or F), we were able to introduce tridentate NHC-amidate-alkoxide palladium(II) complexes. In aqueous solution, these NHC-Pd(II) complexes showed high ability for C-H activation of various hydrocarbons (cyclohexane, cyclopentane, dimethyl ether, THF, acetone, and toluene) under mild conditions.
ABSTRACT
The enyne, ubiquitous in natural products, can be a challenge to generate since these moieties require many synthetic transformations to assemble them. We developed a simpler protocol to construct enynes while we found that this oxidative reaction was tolerant in substrate scope. In addition, the utility of this reaction was demonstrated through the attempt in synthesizing antifungal agent Lamisi.
ABSTRACT
Reported herein is a new approach to prepare biaryl derivatives via a tandem Pd catalyzed boron-Heck and Suzuki reaction. This one-pot tandem process avoided purification or addition of extra catalyst between steps. The resulting biaryl compounds can be prepared with substrate variability in good to moderate yields.
ABSTRACT
Reported herein is a novel approach to the total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid, where the stereochemistries on C(2), C(3), and C(4) of the pyrrolidine core were introduced efficiently and selectively. A regio- and stereoselective C-H insertion reaction was utilized to prepare the gamma-lactam as an intermediate. A Michael-type cyclization of phenylsulfone with a conjugated acetylenic ketone was developed to prepare the tricyclic ketone as a key intermediate for (-)-alpha-kainic acid. Subsequently, a stereoselective dephenylsulfonylation was carried out successfully to secure the cis relationship at C(3) and C(4) centers. An unprecedented acetylation on the phenylsulfone, followed by a stereoselective dephenylsulfonylation, secured the trans relationship at C(3) and C(4) centers in (+)-alpha-allokainic acid.
Subject(s)
Kainic Acid/analogs & derivatives , Kainic Acid/chemical synthesis , Cyclization , Kainic Acid/chemistry , Molecular Conformation , StereoisomerismABSTRACT
Herein, we report an asymmetric intermolecular Heck-type reaction of acyclic alkenes by using a palladium-pyridinyl oxazoline diacetate complex under oxidative palladium(II) catalysis conditions. A premade palladium-ligand complex afforded higher enantioselectivities than a corresponding premixed palladium-ligand system, while offering enhanced asymmetric induction when compared to known intermolecular Heck-type protocols.